Modulation of MUC1 Protein Expression by PPAR‐gamma in Pancreatic Cancer Cells

Abstract

The survival rate of pancreatic cancer is approximately four months. Most pancreatic carcinomas overexpress MUC1. MUC1 is a glycoprotein that serves as a barrier to infection in normal cells. However, MUC1 protects cancer cells from immune responses and cell death. Therefore, reducing MUC1 protein expression is expected to increase the sensitivity of tumor cells to killing by cells of the immune system. PPARs are transcription factors of the nuclear receptor family. PPARγ heterodimerizes with retinoid X receptor and binds to PPAR response elements. Recent studies in our laboratory have shown that rosiglitazone reduces cytokine‐stimulated MUC1 expression in various cancer cell lines. Therefore, we hypothesized that rosiglitazone will reduce MUC1 protein expression in pancreatic cancer cells. Pancreatic cancer cell lines were cultured and serum starved for several days. The cell lines were treated with and without rosiglitazone. Western blotting and autoradiography were used to separate and detect the MUC1 proteins synthesized by the cells. Our results indicate that rosiglitazone significantly reduces MUC1 protein expression in Capan2 and HPAF2 cell lines. PPARγ agonists in combination with tumoricidal agents offer a promising avenue to increase pancreatic tumor cell sensitivity to killing by decreasing MUC1 levels. Funding provided by the HHMI Science Education Grant and the McNair Scholars Program.